Uniting biobank resources reveals novel genetic pathways modulating susceptibility for atopic dermatitis

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:149

Article

Sliz, Eeva^1,2  Huilaja, Laura^3,4,5  Pasanen, Anu^3,4,5,6,7,8  Laisk, Triin⁹  Reimann, Ene⁹  Magi, Reedik⁹  Hannula-Jouppi, Katariina^10,11,12,13  Peltonen, Sirkku^14,15,16,17  Salmi, Teea^18,19  Koulu, Leena^14,15  Tasanen, Kaisa^3,4,5  Kettunen, Johannes^1,2 

[1] Univ Oulu, Ctr Life Course Hlth Res, Fac Med, Aapistie 5A,POB 5000, Oulu 90014, Finland

[2] Univ Oulu, Bioctr Oulu, Oulu, Finland

[3] Med Res Ctr Oulu, Dept Dermatol, PEDEGO Res Unit, Oulu, Finland

[4] Univ Hosp, Oulu, Finland

[5] Univ Oulu, Oulu, Finland

[6] Univ Oulu, PEDEGO Res Unit, Oulu, Finland

[7] Univ Oulu, Med Res Ctr Oulu, Oulu, Finland

[8] Oulu Univ Hosp, Dept Children & Adolescents, Oulu, Finland

[9] Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia

[10] Univ Helsinki, ERN Skin Ctr, Dept Dermatol & Allergol, Helsinki, Finland

[11] Helsinki Univ Cent Hosp, Helsinki, Finland

[12] Folkhalsan Res Ctr, Helsinki, Finland

[13] Univ Helsinki, Res Programs Unit, Stem Cells & Metab Res Program, Helsinki, Finland

[14] Univ Turku, Dept Dermatol & Venereol, Turku, Finland

[15] Turku Univ Hosp, Dept Dermatol, Turku, Finland

[16] Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Dermatol & Venereol, Gothenburg, Sweden

[17] Sahlgrens Univ Hosp, Dept Dermatol & Venereol, Reg Vastra Gotaland, Gothenburg, Sweden

[18] Tampere Univ, Fac Med & Hlth Technol, Celiac Dis Res Ctr, Tampere, Finland

[19] Tampere Univ Hosp, Dept Dermatol, Tampere, Finland

关键词: Atopic dermatitis;    genome-wide association;    DSC1;    SERPINB7;    FinnGen;   

DOI  :  10.1016/j.jaci.2021.07.043

来源: Elsevier

【 摘 要 】

Background: Atopic dermatitis (AD) is a common chronic inflammatory skin disease with high heritability. Previous genome-wide association studies have identified several loci predisposing to AD. These findings explain approximately 30% of the variance in AD susceptibility, suggesting that further work is required to fully understand the genetic underpinnings. Objective: We sought to gain additional understanding of the genetic contribution to AD risk by using biobank resources. Methods: We completed a genome-wide meta-analysis of AD in 796,661 individuals (N-cases = 22,474) from the FinnGen study, the Estonian Biobank, and the UK Biobank. We further performed downstream in silico analyses to characterize the risk variants at the novel loci. Results: We report 30 loci associating with AD (P < 5 x 10(-8)), 5 of which are novel. In 2 of the novel loci, we identified missense mutations with deleterious predictions in desmocollin 1 and serpin family B member 7, genes encoding proteins crucial to epidermal strength and integrity. Conclusions: These findings elucidate novel genetic pathways involved in AD pathophysiology. The likely involvement of desmocollin 1 and serpin family B member 7 in AD pathogenesis may offer opportunities for the development of novel treatment strategies for AD in the future.

【 授权许可】

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